Schlüsselwörter

Ethosuximide in structural-metabolic epilepsy syndromes

Abstract

Ethosuximide is a well-established drug for the treatment of childhood absence epilepsies. In some reports it was also successfully used in other, mostly idiopathic epilepsy syndromes. Its main mechanism of action is blockade of T-type calcium channels but it also exhibits inhibitory effects on G protein-activated inwardly rectifying K+ (GIRK) channels. Animal experiments have shown that anticonvulsant effects are generated in thalamic oscillatory neurons and in some neocortical structures. Moreover, the substance shows antiepileptogenic effects in mouse models of genetic epilepsies. Due to the nearly unique effects (zonisamide shows a weak inhibition of T-type channels too) this drug is an interesting compound in antiepileptic combination therapies. This article presents three cases of severe, pharmacoresistant structural epilepsy where the list of unsuccessfully tried medications showed a gap with regard to T-type calcium channels. Two were adolescents with hypothalamic hamartoma where a long lasting seizure reduction of > 90 % could be achieved by combining lamotrigine and ethosuximide. A third case was a 3-year-old boy with Miller-Dieker syndrome. In this case a massive remission of seizures could be achieved for at least 2 years. In all three cases the effect was accompanied by the disappearance of electroencephalogram (EEG) spike discharges. These case studies show that ethosuximide is a potentially effective agent also in epilepsies with structural etiologies. Its specific mechanisms of action can contribute to polytherapy in highly phramacoresistant epilepsies besides its established indications. Further studies are needed to estimate the chance of a successful treatment under such conditions.